This is an application for a Fogarty International Center K01 International Research Scientist Development Award for Dr. Jennifer Tang, an obstetrician gynecologist specializing in family planning and global women's health at the University of North Carolina (UNC) at Chapel Hill. Dr. Tang is establishing herself as a young investigator in the areas of hormonal contraception and HIV prevention. This K01 award will provide Dr. Tang with the support necessary to accomplish the following goals: (1) to learn the fundamentals of immunological and genital tract markers related to HIV acquisition; (2) to gain experience in advanced study design and biostatistical analysis; (3) to become an expert in the design and implementation of randomized controlled trials in resource-limited settings; and (4) to develop skills in multidisciplinary, long-distance collaboration with clinical and basic scientits. To achieve these goals, Dr. Tang has assembled a mentoring team comprised of a U.S primary mentor, Dr. Jeffrey Stringer, Director of the UNC Global Women's Health Division and an internationally-recognized research expert in HIV prevention and treatment; a Malawi primary mentor, Dr. Mina Hosseinipour, Clinical Director of UNC Project-Malawi and an expert in HIV and infectious disease research in sub-Saharan Africa; Dr. Gretchen Stuart, Director of the UNC Family Planning Program and expert in interactions between hormonal contraception and HIV infection and treatment; Dr. William Miller, Director of the UNC Program in Health Care Epidemiology and Clinical Research and an expert in analytic methods and mentoring young investigators toward research independence; and Dr. Kristina Abel, Associate Director of the UNC Center for AIDS Research Immunology Core and an expert in mucosal immunity and the pathogenesis of HIV infection. Understanding the potential association between progestins (such as medroxyprogesterone or levonorgestrel) and HIV acquisition is currently a critical research priority for women's health researchers and policymakers. Dr. Tang's research will focus on elucidating this relationship by randomizing HIV-negative women to receive the depot medroxyprogesterone acetate (DMPA) injection or the Jadelle(R) levonorgestrel implant and comparing the immunologic changes (Aim 1) and genital tract changes (Aim 2) that occur after initiation of these contraceptives. In addition, her research will evaluate the feasibility and acceptability of conducting a long-term randomized controlled trial of DMPA versus Jadelle(R) in a sub-Saharan African population at-risk for HIV acquisition (Aim 3). Dr. Tang will randomize 30 women to DMPA or Jadelle(R) and evaluate serum and genital tract levels of antimicrobials, inflammatory cytokines, and anti-inflammatory cytokines at multiple time points before and after contraceptive initiation, for up to 2 years of contraceptive use. This study will form the basis fo a larger, multicenter clinical trial that will evaluate the risk for HIV acquisition among women usin DMPA , Jadelle(R), and other hormonal contraceptives. This trial will be submitted by Dr. Tang as an R01 application before the end of the 4-year career development award period.